Hepatoma is a common disease with high morbidity in China and Southeast Asia. Particularly in China, about 110,000 patients die of hepatoma each year, which holds 43% among the total dead hepatoma patients in the world. Therefore, it still requires comprehensive and profound research on hepatoma diagnosis and therapy. A variety of McAbs have been identified since hybridoma technology was established by Kohler and Milstein in 1975. These McAbs shed new light on the preclinical and clinical research and anti-hepatoma McAbs are no exception. In the past 20 years, traditional production of anti-hepatoma antibodies has focused on such target molecules as α-fetoprotein and ferritin. In these processes, traditional immunization methods are adopted, i.e. with the soluble extraction materials of hepatocarcinoma or cultured hepatocarcinoma cells as the immunogen. However, it is difficult to generate anti-hepatoma antibodies with high affinity and specificity by these methods because of the variation, instability or partial loss of the tumor antigenic epitopes.
There are several successful reports on antibody generation using cell suspensions derived from fresh tumor tissue to immunize animals. In spite of the complicated screening, antigenicity can be better retained in this way. The inventors have successfully obtained seven clones of specific anti-hepatoma antibodies using this method. The detailed process for the establishment of these hybridoma cell strains that secret murine anti-hepatoma antibodies is shown in Zhinan Chen, Yanfang Liu, Jizheng Yang et al., McAb Communications, 1989; 2: 33-36. Among these antibodies, anti-human hepatoma McAb HAb18 was found to have higher specificity, with an immunohistochemistry positive rate up to 75%. Starting from anti-human hepatoma McAb HAb18, the inventors have successfully cloned heavy and light chain variable region genes. With the advances of the research of genetically engineered antibody, this invention establishes a solid basis to develop novel small molecule genetically engineered antibody.